Wilson J F, Jenkin R D, Anderson J R, Chilcote R R, Coccia P, Exelby P R, Kersey J, Kjeldsberg C R, Kushner J, Meadows A
Cancer. 1984 Apr 15;53(8):1695-704. doi: 10.1002/1097-0142(19840415)53:8<1695::aid-cncr2820530813>3.0.co;2-u.
Between April 1977, and August 1980, the Children's Cancer Study Group (CCSG) conducted a clinical trial of childhood non-Hodgkin's lymphoma (NHL), randomizing 256 patients to one of two treatment regimens. A 4-drug regimen (regimen 1, modified cyclophosphamide, Oncorin [vincristine], methotrexate, prednisone [COMP] ) was compared with a 10-drug regimen (regimen 2, modified LSA2-L2). Using the Rappaport classification, the review pathologist diagnosed the 213 evaluable tissue specimens as follows: lymphoblastic (LC), 73; Burkitt's tumor (BT), 40; "undifferentiated" non-Burkitt's type (NB), 67; large cell or "histiocytic" lymphoma (HI), 29; and other types (OT), 4. Concurrence in classification between the review and institutional pathologists was poor when using the above four categories; however, concurrence was 88% between the review pathologist and other hematopathologists, and 99% when classifying the specimens as lymphoblastic or nonlymphoblastic. For patients with nonlocalized disease, this randomized controlled study demonstrated a new important correlation of histopathology with the effectiveness of treatment. When analyzed without stratification into lymphoblastic and nonlymphoblastic types, the two regimens showed identical relapse free survival (RFS) curves for patients with nonlocalized involvement. However, when patients were stratified according to histologic classification, regimen 2 was superior to regimen 1 for patients with lymphoblastic lymphoma, achieving 74% RFS at 30 months compared to 31% for regimen 1 (P = 0.001). Conversely, those with nonlymphoblastic types (BT, NB, HI) treated with regimen 1 had a 58% RFS at 30 months compared to 32% for those treated on regimen 2 (P = 0.01). This study demonstrates that proper, routine histopathologic classification of NHL is the best criterion for choice of therapy in children with nonlocalized involvement. As a result of this study, all patients with nonlocalized disease, diagnosed after August 1980, were no longer randomized but were assigned to the appropriate treatment regimen based on prospective review of histopathology.
1977年4月至1980年8月期间，儿童癌症研究组（CCSG）开展了一项儿童非霍奇金淋巴瘤（NHL）的临床试验，将256名患者随机分为两种治疗方案之一。将一种4药方案（方案1，改良环磷酰胺、安可宁[长春新碱]、甲氨蝶呤、泼尼松[COMP]）与一种10药方案（方案2，改良LSA2-L2）进行比较。采用Rappaport分类法，复审病理学家将213份可评估的组织标本诊断如下：淋巴母细胞型（LC）73例；伯基特肿瘤（BT）40例；“未分化”非伯基特型（NB）67例；大细胞或“组织细胞”淋巴瘤（HI）29例；其他类型（OT）4例。当使用上述四类进行分类时，复审病理学家与机构病理学家之间的分类一致性较差；然而，复审病理学家与其他血液病理学家之间的一致性为88%，将标本分类为淋巴母细胞型或非淋巴母细胞型时一致性为99%。对于患有非局限性疾病的患者，这项随机对照研究证明了组织病理学与治疗效果之间一种新的重要关联。在未分层为淋巴母细胞型和非淋巴母细胞型的情况下进行分析时，对于患有非局限性病变的患者，两种方案显示出相同的无复发生存（RFS）曲线。然而，当根据组织学分类对患者进行分层时，对于淋巴母细胞淋巴瘤患者，方案2优于方案1，在30个月时的无复发生存率达到74%，而方案1为31%（P = 0.001）。相反，接受方案1治疗的非淋巴母细胞型（BT、NB、HI）患者在30个月时的无复发生存率为58%，而接受方案2治疗的患者为32%（P = 0.01）。这项研究表明，对NHL进行恰当的常规组织病理学分类是选择治疗非局限性病变儿童的最佳标准。由于这项研究，1980年8月以后诊断出患有非局限性疾病的所有患者不再进行随机分组，而是根据组织病理学的前瞻性复审被分配到适当的治疗方案中。
